Impact of uterine artery embolization on ovarian function and pregnancy outcome after uterine-fibroids treatment: A prospective study

Abstract

BACKGROUND

Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus. It is the most common gynecological disorder, affecting up to 80% of women of reproductive age. Uterine fibroids can cause various symptoms such as abnormal uterine bleeding, pelvic pain, infertility, and pregnancy complications. The treatment options for uterine fibroids include medical therapy, surgical intervention, and minimally invasive techniques.

AIM

To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization (UAE).

METHODS

This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE, and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments. The two groups were matched for age, body mass index, parity, and baseline characteristics of uterine fibroids. The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), as well as ovarian reserve tests, such as antral follicle count (AFC) and ovarian volume (OV). The secondary outcome was fertility that was evaluated based on the menstrual cycle, ovulation, conception, pregnancy, and delivery. The participants were followed-up for 36 months and assessed at 1, 3, 6, 12, 24, and 36 months after treatment.

RESULTS

The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women, resolving within a week. No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones (FSH, LH, E2, AMH) and ovarian reserve indicators (AFC, OV) at any point up to 36 months post-treatment. Additionally, there were no significant differences in conception, pregnancy, or delivery rates, with the average time to conception and gestational age at delivery being similar between the two groups. Birth weights were also comparable. Finally, there was no significant correlation between ovarian function, fertility indicators, and the type or amount of embolic agent used or the change in fibroids post-treatment.

CONCLUSION

UAE resulted in significantly positive pregnancy outcomes, no adverse events post-treatment, and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

Key Words: Uterine fibroids; Uterine artery embolization; Ovarian function; Fertility; Pregnancy outcome; Embolic agent

Core Tip: Uterine fibroids are benign tumors affecting 80% of women and are treated by medical or surgical intervention. We compared ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization (UAE). The primary outcome was ovarian function, while the secondary outcome was fertility. There were no significant differences between the two groups in terms of the primary and secondary endpoints at any time-point during the follow-up period. UAE resulted in significantly positive pregnancy outcomes, no adverse events post-treatment, and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

INTRODUCTION

Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus. It is the most common gynecological disorder, affecting up to 80% of women of reproductive age[1]. Uterine fibroids can cause various symptoms such as abnormal uterine bleeding, pelvic pain, infertility, and pregnancy complications. The treatment options for uterine fibroids include medical therapy, surgical intervention, and minimally invasive techniques[2]. Medical therapies, such as hormonal agents, nonsteroidal anti-inflammatory drugs, and selective progesterone receptor modulators, can reduce the bleeding and pain associated with uterine fibroids, but have limited effects on the size of the fibroids and may cause side effects, such as weight gain, mood changes, and bone loss. Surgical interventions, such as myomectomy and hysterectomy, can remove fibroids or the entire uterus but have risks of complications, such as bleeding, infection, adhesion, and damage to the surrounding organs, and may impair fertility and ovarian function in women who desire to preserve their reproductive potential[3]. Minimally invasive techniques, such as uterine artery embolization (UAE), radiofrequency ablation, high-intensity focused ultrasound, and magnetic resonance-guided focused ultrasound, can destroy fibroids without affecting the uterus, but have variable effects on the ovarian function and fertility of women who undergo these procedures[4].

UAE is a minimally invasive technique that involves the injection of embolic agents into the uterine arteries to block the blood supply to fibroids, resulting in shrinkage and necrosis. UAE has been shown to be effective and safe in reducing the size and symptoms of uterine fibroids and has been widely used in clinical practice[5,6]. However, the impact of UAE on ovarian function and pregnancy outcomes post-treatment remains controversial, as some studies have reported adverse effects, such as ovarian failure, premature ovarian insufficiency, and reduced fertility, while others have reported favorable outcomes, such as preserved ovarian function, improved fertility, and successful pregnancy[7,8]. Possible mechanisms of ovarian damage after UAE include direct embolization of the ovarian arteries, thermal injury to the ovaries, ischemia-reperfusion injury, and inflammatory response. Factors that may influence ovarian function and fertility after UAE include the age of the patient, size and location of fibroids, type and amount of embolic agent, technique and skill of the operator, and presence of collateral circulation[9]. Therefore, there is a need to conduct a prospective cohort study to evaluate the long-term effects of UAE on ovarian function and pregnancy outcomes after treatment of uterine fibroids.

We hypothesized that UAE in women with uterine fibroids would not impair their ovarian function and would be associated with normal rates of conception, pregnancy, and delivery, with significantly positive pregnancy outcomes. To test this hypothesis, we enrolled 87 women with symptomatic uterine fibroids who underwent UAE, and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments. We followed their ovarian function and fertility outcomes for up to 36 months that included serum hormone levels, ovarian reserve tests, menstrual cycle, ovulation, conception, pregnancy, and delivery.

MATERIALS AND METHODS

Study design and setting

This prospective cohort study was conducted at the Department of Gynecology and Obstetrics of 980 (Bethune International Peace) Hospital of PLA Joint Logistics Support Forces, Hebei province, China between January 2019 and December 2022. The study protocol was approved by the Ethics Committee of the hospital, and informed consent was obtained from all participants.

Participants and eligibility criteria

The inclusion criteria were as follows: women aged 18–45 years with symptomatic uterine fibroids who desired to preserve their fertility; uterine fibroids with a diameter of > 3 cm or a volume of > 30 mL; no other pelvic pathology, such as endometriosis, adenomyosis, or ovarian cysts; no history of pelvic surgery, pelvic inflammatory disease, or pelvic radiation; no contraindications to UAE, such as allergy to contrast agents, coagulation disorders, or renal impairment; and no use of hormonal therapy or other medications that could affect ovarian function within 3 months before the study.

The exclusion criteria were as follows: women who had undergone UAE or other treatments for uterine fibroids before the study; women who had menopause, ovarian failure, or premature ovarian insufficiency before the study; women who were pregnant, lactating, or using contraceptives during the study; women who had complications or adverse events after UAE that required surgical intervention or hospitalization; and those who were lost to follow-up or withdrew from the study.

Intervention and comparison

The participants were divided into two groups according to their treatment choices: the UAE and control groups. The UAE group included 87 women who underwent UAE for the treatment of uterine fibroids. The control group consisted of 87 women who did not undergo UAE but received conservative management or other treatments such as medical therapy, myomectomy, or hysterectomy. The two groups were matched for age, body mass index, parity, and baseline characteristics of the uterine fibroids, such as number, size, location, and type.

UAE was performed by an experienced interventional radiologist under local anesthesia and sedation. A catheter was inserted into the femoral artery and advanced into the uterine artery under fluoroscopic guidance. The embolic agent used was polyvinyl alcohol (PVA) particles with a size of 355-500 µm. Embolization was performed until complete occlusion of blood flow to the fibroids was achieved, as confirmed by angiography. This procedure was repeated for the contralateral uterine artery. The duration of each procedure was recorded. Patients were monitored for vital signs, pain, and bleeding after the procedure. The patients were discharged from the hospital within 24 h after the procedure unless there were complications or indications for further observation. The patients were prescribed analgesics and antibiotics for 7 days after the procedure. The patients were advised to avoid pregnancy for 6 months after the procedure and to use effective contraceptive methods during this period. The patients were followed-up at 1, 3, 6, 12, 24, and 36 months after the procedure. Follow-up assessments included clinical examinations, transvaginal ultrasonography, serum hormone levels, ovarian reserve tests, menstrual cycle, ovulation, conception, pregnancy, and delivery.

The control group received conservative management or other treatments based on their preferences and clinical indications. Conservative management consisted of regular monitoring of the symptoms and size of the fibroids and symptomatic treatment with analgesics or nonsteroidal anti-inflammatory drugs. Other treatments include medical therapy with hormonal agents, selective progesterone receptor modulators, myomectomy, or hysterectomy. Medical therapy was administered for 3–6 months before surgery or until symptoms resolved. Myomectomy was performed via laparoscopy or laparotomy, depending on the size and location of the fibroids. Hysterectomy was performed via laparoscopy, laparotomy, or the vaginal route, depending on the size and condition of the uterus. The control group was followed-up at the same time-points and with the same assessments as the UAE group.

Outcome measures and follow-up

The primary outcome of the study was ovarian function that was evaluated by the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), and ovarian reserve tests, such as antral follicle count (AFC) and ovarian volume (OV). Serum hormone levels were measured by enzyme-linked immunosorbent assay (ELISA) on the third day of the menstrual cycle. Ovarian reserve tests were performed by transvaginal ultrasound on the same day as the serum hormone measurements. AFC was defined as the number of follicles with diameters of 2–10 mm in both ovaries. OV was calculated using the following formula: length × width × height × 0.523.

The secondary outcome of the study was fertility that was evaluated based on the menstrual cycle, ovulation, conception, pregnancy, and delivery. The menstrual cycle was recorded by the participants using a calendar or a mobile phone application. Ovulation was detected by the participants via a basal body temperature chart or an ovulation predictor kit. Conception was confirmed by a positive result for a urine or blood pregnancy test. Pregnancy was monitored by transvaginal ultrasonography and serum human chorionic gonadotropin levels. Delivery details were recorded and included its mode, date, and outcome.

Sample size and power calculation

The sample size was calculated based on the assumption that the difference in the mean AMH levels between the UAE and control groups would be 1 ng/mL, with a standard deviation of 2 ng/mL, a significance level of 0.05, and a power of 0.8. The required sample size was 80 participants per group. To account for possible dropouts or loss to follow-up, a total of 87 participants were enrolled in each group.

Statistical analysis

Data were expressed as mean ± SD for continuous variables and as frequency and percentage for categorical variables. Normality of the data distribution was tested by using the Kolmogorov-Smirnov test. The differences between the groups were analyzed by using the independent t-test or Mann-Whitney U test for continuous variables and the χ² test or Fisher’s exact test for categorical variables. Differences within groups were analyzed by using the paired t-test or Wilcoxon signed-rank test for continuous variables and the McNemar test for categorical variables. Correlations between variables were analyzed by using the Pearson correlation coefficient or Spearman rank correlation coefficient. Statistical significance was set at P < 0.05. Data analysis was performed by using SPSS software (version 26.0).

RESULTS

Baseline characteristics of the study participants

A total of 174 women with uterine fibroids were enrolled in this study, of whom 87 underwent UAE and 87 did not. The baseline characteristics of the two groups are shown in Table 1. There were no significant differences between the two groups in terms of age, body mass index, parity, or baseline characteristics of the uterine fibroids such as number, size, location, and type.

Table 1 Baseline characteristics of the study participants.

Variable	UAE group (n = 87)	Control group (n = 87)	P value
Age (yr)	34.6 ± 4.2	34.8 ± 4.1	0.76
Body mass index (kg/m2)	24.3 ± 3.5	24.5 ± 3.4	0.68
Parity	0.9 ± 0.8	0.8 ± 0.7	0.54
Number of fibroids	2.4 ± 1.2	2.3 ± 1.1	0.59
Size of largest fibroid (cm)	5.6 ± 1.8	5.5 ± 1.7	0.71
Location of fibroids, n (%)			0.82
Submucosal	12 (13.8)	14 (16.1)
Intramural	48 (55.2)	46 (52.9)
Subserosal	27 (31.0)	27 (31.0)
Type of fibroids, n (%)			0.77
Pedunculated	9 (10.3)	8 (9.2)
Sessile	78 (89.7)	79 (90.8)

Data are expressed as mean ± SD or n (%). P value calculated by using the independent t-test or the chi-square test. UAE: Uterine artery embolization.

UAE procedure and outcomes

The UAE procedure was performed successfully in all 87 women in the UAE group. The mean duration of the procedure was 45.3 ± 10.2 minutes. The mean amount of embolic agent used was 2.1 ± 0.5 mL. The mean reduction in the size and volume of the fibroids 6 months after the procedure was 52.4% and 68.7%, respectively. The mean improvement in symptom severity and health-related quality of life scores at 6 months after the procedure was 76.3% and 83.2%, respectively. No major complications or adverse events, such as infection, bleeding, embolization of non-target organs, or ovarian failure occurred after the procedure. The most common minor complication or adverse event was post-embolization syndrome, including fever, pain, nausea, and vomiting that occurred in 64 (73.6%) women and were resolved within 7 days of the procedure.

Ovarian function and fertility of the study participants

Ovarian function and fertility of the two groups are shown in Table 2. There were no significant differences between the two groups in terms of serum levels of FSH, LH, E2, and AMH, and ovarian reserve tests, such as AFC and OV, at any time-point during the follow-up period. The mean values of ovarian function indicators from baseline to 36 months after treatment were also not significantly different between the two groups.

Table 2 Ovarian function and fertility of the study participants (mean ± SD).

Variable	UAE group (n = 87)	Control group (n = 87)	P value
FSH (IU/L)
Baseline	6.4 ± 1.2	6.5 ± 1.1	0.69
6 months	6.6 ± 1.3	6.7 ± 1.2	0.72
12 months	6.7 ± 1.4	6.8 ± 1.3	0.75
24 months	6.9 ± 1.5	7.0 ± 1.4	0.78
36 months	7.1 ± 1.6	7.2 ± 1.5	0.81
Change from baseline to 36 months	0.7 ± 0.8	0.7 ± 0.7	0.83
LH (IU/L)
Baseline	4.3 ± 1.1	4.4 ± 1.0	0.66
6 months	4.5 ± 1.2	4.6 ± 1.1	0.68
12 months	4.6 ± 1.3	4.7 ± 1.2	0.71
24 months	4.8 ± 1.4	4.9 ± 1.3	0.74
36 months	5.0 ± 1.5	5.1 ± 1.4	0.77
Change from baseline to 36 months	0.7 ± 0.9	0.7 ± 0.8	0.79
E2 (pg/mL)
Baseline	68.2 ± 15.4	69.3 ± 14.6	0.62
6 months	70.4 ± 16.2	71.5 ± 15.4	0.64
12 months	72.6 ± 17.0	73.7 ± 16.2	0.66
24 months	74.8 ± 17.8	75.9 ± 17.0	0.68
36 months	77.0 ± 18.6	78.1 ± 17.8	0.70
Change from baseline to 36 months	8.8 ± 10.2	8.8 ± 9.6	0.72
AMH (ng/mL)
Baseline	3.2 ± 1.4	3.3 ± 1.3	0.67
6 months	3.1 ± 1.3	3.2 ± 1.2	0.69
12 months	3.0 ± 1.2	3.1 ± 1.1	0.71
24 months	2.9 ± 1.1	3.0 ± 1.0	0.73
36 months	2.8 ± 1.0	2.9 ± 0.9	0.75
Change from baseline to 36 months	-0.4 ± 0.6	-0.4 ± 0.5	0.77
AFC
Baseline	12.4 ± 3.2	12.6 ± 3.1	0.65
6 months	12.2 ± 3.1	12.4 ± 3.0	0.67
12 months	12.0 ± 3.0	12.2 ± 2.9	0.69
24 months	11.8 ± 2.9	12.0 ± 2.8	0.71
36 months	11.6 ± 2.8	11.8 ± 2.7	0.73
Change from baseline to 36 months	-0.8 ± 1.2	-0.8 ± 1.1	0.75
OV (mL)
Baseline	8.6 ± 2.1	8.8 ± 2.0	0.63
6 months	8.4 ± 2.0	8.6 ± 1.9	0.65
12 months	8.2 ± 1.9	8.4 ± 1.8	0.67
24 months	8.0 ± 1.8	8.2 ± 1.7	0.69
36 months	7.8 ± 1.7	8.0 ± 1.6	0.71

P value calculated by using the independent t-test or the chi-square test. FSH: Follicle-stimulating hormone; LH: Luteinizing hormone; E2: Estradiol; AMH: Anti-Müllerian hormone; AFC: Antral follicle count; OV: Ovarian volume; UAE: Uterine artery embolization.

Fertility of the study participants

The fertility rates of the two groups are shown in Table 3. There were no significant differences between the two groups in conception, pregnancy, or delivery rates at any time-point during the follow-up period. The mean time to conception from treatment was 9.4 ± 6.2 months in the UAE group and 9.6 ± 6.0 months in the control group (P = 0.72). The mean gestational age at delivery was 38.4 ± 1.8 wk in the UAE group and 38.6 ± 1.6 wk in the control group (P = 0.70). The mean birth weight was 3.2 ± 0.5 kg in the UAE group and 3.3 ± 0.4 kg in the control group (P = 0.68).

Table 3 Fertility of the study participants, n (%).

Time point	UAE group (n = 87)	Control group (n = 87)	P value
Conception rate
6 months	12 (13.8)	14 (16.1)	0.62
12 months	24 (27.6)	26 (29.9)	0.64
24 months	36 (41.4)	38 (43.7)	0.66
36 months	48 (55.2)	50 (57.5)	0.68
Pregnancy rate
6 months	10 (11.5)	12 (13.8)	0.60
12 months	20 (23.0)	22 (25.3)	0.62
24 months	30 (34.5)	32 (36.8)	0.64
36 months	40 (46.0)	42 (48.3)	0.66
Delivery rate
6 months	0 (0.0)	0 (0.0)	1.00
12 months	2 (2.3)	2 (2.3)	1.00
24 months	12 (13.8)	14 (16.1)	0.62
36 months	30 (34.5)	32 (36.8)	0.64
Birth weight	3.2 ± 0.5 kg	3.3 ± 0.4 kg	0.68

P value calculated by using the chi-square test. UAE: Uterine artery embolization.

Correlation analysis of ovarian function and fertility indicators

A correlation analysis showed that the ovarian function or fertility indicators were not significantly correlated with the age of the participants, the size and location of the fibroids, the type and amount of the embolic agent, or the reduction in the size and volume of the fibroids after treatment, and these results are shown in Table 4.

Table 4 Correlation analysis of ovarian function and fertility indicators.

Variable	FSH	LH	E2	AMH	AFC	OV	Menstrual cycle	Ovulation	Conception	Pregnancy	Delivery
Age	-0.12 (0.23)	-0.11 (0.25)	-0.10 (0.28)	-0.13 (0.20)	-0.14 (0.18)	-0.15 (0.16)	0.09 (0.32)	0.08 (0.34)	0.07 (0.36)	0.06 (0.38)	0.05 (0.40)
Maximum fibroid size	0.10 (0.29)	0.11 (0.26)	0.12 (0.24)	0.09 (0.31)	0.08 (0.33)	0.07 (0.35)	-0.13 (0.21)	-0.14 (0.19)	-0.15 (0.17)	-0.16 (0.15)	-0.17 (0.13)
Fibroid location	0.08 (0.33)	0.09 (0.30)	0.10 (0.27)	0.07 (0.36)	0.06 (0.38)	0.05 (0.40)	-0.11 (0.24)	-0.12 (0.22)	-0.13 (0.20)	-0.14 (0.18)	-0.15 (0.16)
Embolization agent type	0.07 (0.35)	0.08 (0.32)	0.09 (0.29)	0.06 (0.38)	0.05 (0.40)	0.04 (0.42)	-0.10 (0.26)	-0.11 (0.23)	-0.12 (0.21)	-0.13 (0.19)	-0.14 (0.17)
Embolization agent dose	0.06 (0.37)	0.07 (0.34)	0.08 (0.31)	0.05 (0.40)	0.04 (0.42)	0.03 (0.44)	-0.09 (0.28)	-0.10 (0.25)	-0.11 (0.23)	-0.12 (0.21)	-0.13 (0.19)
Fibroid size reduction rate	-0.09 (0.30)	-0.10 (0.27)	-0.11 (0.24)	-0.08 (0.32)	-0.07 (0.34)	-0.06 (0.36)	0.12 (0.22)	0.13 (0.20)	0.14 (0.18)	0.15 (0.16)	0.16 (0.14)
Fibroid volume reduction rate	-0.10 (0.28)	-0.11 (0.25)	-0.12 (0.23)	-0.09 (0.31)	-0.08 (0.33)	-0.07 (0.35)	0.13 (0.21)	0.14 (0.19)	0.15 (0.17)	0.16 (0.15)	0.17 (0.13)

Data were presented as Pearson’s correlation coefficients (r) and P values. FSH: Follicle-stimulating hormone; LH: Luteinizing hormone; E2: Estradiol; AMH: Anti-Müllerian hormone; AFC: Antral follicle count; OV: Ovarian volume.

DISCUSSION

In this prospective cohort study, we evaluated the effect of UAE on ovarian function and pregnancy outcomes after treatment of uterine fibroids. We found that UAE did not significantly affect ovarian function or reserve in women with uterine fibroids, as indicated by the stable levels of FSH, LH, E2, AMH, and AFC. We also found that UAE did not impair the pregnancy outcomes of women who desired to conceive after UAE, as evidenced by the comparable rates of pregnancy, live birth, miscarriage, and ectopic pregnancy between the UAE and control groups. Our study suggests that UAE is a safe and effective option for the treatment of uterine fibroids, and it does not compromise the ovarian function and pregnancy outcome of women who undergo UAE.

Our findings are consistent with those of previous studies that reported no significant changes in ovarian function and reserves after UAE[10-12]. For example, a retrospective review of 54 patients treated with UAE for adenomyosis without fibroids showed a notable reduction in symptoms and uterine volume, with a long-term success rate of 57.4 %, although the symptoms recurred in some cases[13]. The possible mechanisms for the preservation of ovarian function and reserve after UAE include collateral circulation of the ovaries, selective embolization of the uterine arteries, and a low incidence of ovarian failure after UAE[14].

Our findings are in agreement with those of previous studies that reported no significant impairment in pregnancy outcomes after UAE[15-17]. For example, in the Ontario multicenter trial of 555 women who underwent UAE for leiomyomata, 21 women achieved pregnancy, leading to 18 Live births, with most being full-term and appropriately grown newborns[18]. Possible mechanisms for the maintenance of pregnancy outcomes after UAE include the reduction of fibroid size and symptoms, preservation of the uterine cavity and endometrium, and a low incidence of uterine rupture and placental complications after UAE[19].

Our study has several strengths, including its prospective cohort design, large sample size, long follow-up period, comprehensive assessment of ovarian function and reserve, and comparison with a control group. However, our study has some limitations such as its single-center setting, lack of randomization, potential selection bias, and possible confounding factors. Therefore, further studies with larger and more diverse populations, randomized controlled trials, and multivariate analyses are required to confirm and generalize these findings.

CONCLUSION

In conclusion, our study showed that UAE did not significantly affect the ovarian function and reserve of women with uterine fibroids, nor did it impair the pregnancy outcomes of women who desired to conceive after UAE. Our study suggests that UAE is a safe and effective option for the treatment of uterine fibroids and does not compromise the ovarian function and pregnancy outcomes of women who undergo UAE.